Biosimilar Step Therapy for Medicare Part B: Does This Make Sense?

The Centers for Medicare and Medicaid Services (CMS) has decided drugs covered under Medicare part B may be subject to step therapy, if so desired by Medicare Advantage plans. UnitedHealthcare has become the first to publicly implement step therapy policies for these drugs. However, biosimilar step therapy is not the typical utilization management tool that industry executives are used to seeing.

biosimilar step therapyTraditional step therapy or step edits for prior authorization policies are typically used to require the use of an effective, low-cost drug class before trying a more-expensive treatment. For example, a plan might have a step in place before a patient can receive Humira®, such as requiring documented failure on other disease-modifying anti-rheumatic drugs, like azathioprine or methotrexate. This makes very good sense when supported by practice guidelines or treatment pathways, based on solid supportive evidence.

For biosimilar manufacturers, the perspective on the revised CMS policy, seems to imply trying the biosimilar before receiving the branded originator product. This biosimilar step therapy would make very little sense. A doctor would not be practicing evidence-based medicine if he or she prescribed Remicade® to a patient after failure of Renflexis®. There is no evidence to show that the biosimilar will work in a patient who did not receive adequate clinical benefit from the reference product (and vice versa). Similarly, there is no information to show that a patient who has an adverse effect while taking Remicade will not have that adverse effect after injecting with Renflexis (or vice versa). In other words, after failing one, a new mechanism of action should be tried, not a product with a very similar structure. This may be a different argument, if a subcutaneous form of infliximab was introduced, and this might be reason to step the infusible form through this drug.

In United’s announcement, they are clearly seeking to increase biosimilar utilization, as designated preferred part B agents, at the expense of Remicade use, the nonpreferred agent. Therefore, it may make more sense that new patients will have to use a biosimilar before being prescribed the reference product. Step therapy in this case is almost an aside.

Ironically, the Department of Health and Human Services has also expressed its desire to move part B agents like self-administered injectables to part D. This may not apply to infliximab, as it is given as an in-office infusion. Should this be the case, plans will have many pharmacy tools at their disposal beyond biosimilar step therapy.

In other biosimilar news…Fresenius Kabi has signed an agreement with Abbvie to delay its adalimumab biosimilar market entry in the US until 2023. The manufacturer is currently trying to secure European approval for the product. A 351(k) application has not yet been filed by Fresenius in the US.

Plans Use Step Therapy to Encourage Utilization of Remicade Over Biosimilars

Health plans and insurers are not yet turning to biosimilar infliximab as a preferred therapy, according to Gillian Woollett, DPhil, MA, of Avalere. Her new report surveyed publicly available policy about health plans across the nation. The principal finding was that step therapy was commonly used  to encourage use of the originator product.

In fact, just one health plan (representing 1% of the 172 million lives covered in this study) supported the use of either Inflectra® or Renflexis® over the reference product Remicade® through step therapy. One plan (2% of the covered lives) allowed the use of either the originator product or Inflectra as a first step.

Gillian Woollett of Avalere on step therapy and biosimilars
Gillian Woollett

Four of the 18 plans with publicly available information did not utilize step-therapy rules for any forms of infliximab. However, “10 of the 18 plans (55% of plans, 52% of covered lives) require the use of [Remicade] first, alone or in combination with another DMARD,” stated Dr. Woollett in the report. A total of 81% of the covered lives from these 18 plans were subject to step therapies limiting access to one infliximab product or the other.

On its face, this type of step policy makes a bit of sense. Step therapies are often used alone or part of prior authorization mechanisms to make sure patients try more cost-effective agents first. In rheumatoid arthritis, that may comprise use of nonbiologic drugs before proceeding to a TNF inhibitor and then to another biologic in patients with rheumatoid arthritis. However, there is no proven benefit (or even logic) to offering a biosimilar infliximab after failing Remicade, or vice versa. If there was a significant clinically relevant difference in immunogenicity, this could be an issue, but this also has not been seen in practice. It makes more sense to try another anti-TNF or perhaps even move to an interleukin inhibitor—something with a different (or slightly different) mode of action.

A policy such as this can confuse the issue for patients, whose knowledge of biosimilars seems tenuous, and even providers, some of whom have little experience prescribing them, particularly because of payers’ Remicade-first policies.

The Avalere report provides some support for how payers are arresting utilization of biosimilar infliximab in favor of the originator infliximab product.

Dr. Woollett paints a very different picture for subcutaneously administered filgrastim products. Forty-nine percent of the covered lives (five large plans) had policies favoring Zarxio®, whereas 27% of covered lives were encouraged to use Neupogen® first.  For these 18 plans, five (28% of plans, 49% of covered lives) demonstrate a preference for the biosimilar, filgrastim-sndz. Five (28% of plans, 27% of covered lives) demonstrate a preference for the reference filgrastim. Eight plans (44% of plans, 24% of covered lives) do not indicate a preference through formulary design. A further 24% were not subject to any preference.

Evidence to Support Zarxio Use Presented at AMCP

Two posters presented at the Academy of Managed Care Pharmacy bolstered the case for moving away from the use of the originator filgrastim product Neupogen®.

In a study from Magellan Rx Management, Scottsdale, AZ, the researchers grouped both Zarxio® and Granixzarxio® together as alternatives to the originator filgrastim in the granulocyte-colony-stimulating factor (G-CSF) category as supportive oncological care. They studied the effect of a step edit, requiring the use of either Zarxio or Granix first, and its effect on utilization trends and cost savings among 2.7 million covered lives.

The step edit was implemented in October 2016 and the results for the fourth quarter of 2016 were compared with utilization and cost data from the first three quarters of that year. In terms of utilization, the marketshare of Neupogen dropped from 18% in early 2016 to only 2% by the third quarter of 2017. As expected, the drop in utilization occurred just after the step edit was introduced a year ago. The combined marketshare of Granix and Zarxio jumped from 9% to 21% over that time, but the dominant player in the G-CSF space, Neulasta® (pegfilgrastim), maintained utilization, rising from 73% to 77%. Over the one-year period since the step edit was introduced, the authors calculated a cost savings of $662,278; the cost savings in the quarter after the policy change was $106,980, or approximately 8% of the total spent for the G-CSF category.

The authors noted that the cost savings were calculated using wholesale acquisition cost (WAC) not average sales price (ASP), and manufacturer discounts or rebates were not considered in the estimates.

The second poster, sponsored by Sandoz, was a retrospective claims analysis of the incidence of febrile neutropenia in patients receiving chemotherapy who were treated with Zarxio or Neupogen. This study covered 13 months of claims (from Optum) from 162 patients taking Zarxio compared with 3,297 receiving Neupogen. The groups did not differ significantly in terms of demographics, insurance, or tumor type.

The researchers found that the incidence of neutropenia (in addition to fever and/or infection) was nonsignificantly greater in those receiving the biosimilar compared with the reference product (2.3% vs. 1.7%, respectively).